Fibrinogen applications

Figure 4.20 Product-ion MS-MS spectrum from the doubly charged molecular ion of the peptide glu-fibrinogen B generated during electrospray ionization. From applications literature published by Thermofinnigan, Hemel Hempstead, UK, and reproduced with permission.

W. L., and Rivera, K. E., Facile purification of fibrinogen fragments using a computer-based model with general applicability to the generation of salt gradients, Prot. Expression Purif., 14, 71, 1998. 

The most widely studied synthetic polymers for blood contact applications are polyether urethane ureas ( Biomer (Ethicon)). These materials have been used in artificial hearts, as coatings for lead wires in pacemakers, have been used and are being considered for blood vessel prostheses. The success of these materials is believed to be due to preferential adsorption of albumin rather than globulin or fibrinogen which promote a clotting response. However, these materials are hydrophobic and questions of long-term effectiveness are unresolved. Particularly, these materials may shed emboli or may be susceptible to surface calcification. Thus, it may be desirable to have synthetic polymers which are hydrophilic and better resemble blood vessels [475]. 

Weisel, J. W., and Cederholm-Williams, S. A. (1997). Fibrinogen and fibrin Characterization, processing and medical applications. In Handbook of Biodegradable Polymers (A. J. Domb, J. Kost, and D. M. Wiseman, Eds.), pp. 347-365. Harwood, Amsterdam. 

Using the cage implant system, Kim et al. successfully polymerized a phospholipid on to a solid substrate and found reduced adsorption of proteins such as albumin, fibrinogen, and IgG and also reduced macrophage adhesion.80 There has also been widespread interest in the use of PC coats for orthopedic joint implants as well as other biomedical applications.81 3... 

For thin rods of length /, it can be shown that L = 112 [27]. Estimate K for fibrinogen, which can be approximated as a thin rod of length 700 A, partitioning into a porous solid with s = 0.012/A. What does K change to if all pore dimensions are exactly doubled in size Assume the applicability of the random-plane model of pore space. 

S-FFF has successfully been applied to separate and characterize a number of biopolymers, including DNA [176,369], proteoglycans [370], cartilage proteoglycans [371],dextrans [141] and fibrinogen [176]. Further applications concerned preparative S-FFF of DNA-plasmid from crude cellular lysates [372]. 

Three types of plasticised PVC containing either diethylhexyl phthalate, triethylhexyl trimellitate or butyltrihexyl citrate as plasticisers were assessed for blood contacting applications. Correlations between plasticiser and fibrinogen adsorption behaviour are discussed. The fibrinogen adsorption mechanism was also examined using Freundlich adsorption modelling. 11 refs. 

A study has been carried out on the interactions of blood with plasticised poly(vinyl chloride) biomaterials in a tubular form. The influence of different factors such as the biomaterial, antithrombotic agent, blood condition and the nature of the application is represented when considering the blood response in the clinical utilisation of the plasticised PVC. The PVC was plasticised with di-(2-ethylhexyl)phthalate (DEHP) and tri-(2-ethylhexyl)trimellitate (TEHTM)and in-vitro and ex-vivo procedures used to study the biomaterial with respect to the selection of the plasticiser. The blood response was measured in terms of the measurement of fibrinogen adsorption capacity, thrombin-antithrombin III complex and the complement component C3a. X-ray photoelectron spectroscopy was used for surface characterisation of the polymers and the data obtained indicated that in comparison with DEHP-PVC, there is a higher reactivity... 

Some of the applications that fall clearly into this category are imaging of DNA on mica (3) and imaging of catalase (a globular protein) as well as fibrinogen (a filamentous protein) on a SAM-coated Au layer (7). Another review (45) is suggested to the interested reader for experimental details and for a more complete list of investigated biomolecules. 

In vivo, the infusion of small amounts of thrombin (<200 NIH-U/kg/h) causes defibrinogenation. Because of the slow transformation of fibrinogen, the fibrin monomers formed are eliminated via reactive fibrinolysis and RES without precipitation of fibrin. Upon infusion of higher amounts of thrombin, these clearance mechanisms fail to offset the thrombin action, which then leads to the formation of microthrombi in the peripheral circulation. Correspondingly, the bolus injection of 1500 NIH-U thrombin/kg caused death of the experimental animals. However, a bolus injection of benzoyl-thrombin at a dose corresponding to the amount of 1500 NIH-U/kg caused defibrinogenation only. Therefore, bolus application of acyl-thrombin may initiate an infusion regimen [26]. 

Fibrinogen Receptor Antagonists Design and Clinical Applications... 

---